A state of chronic hypocholesterolemia is present in myeloproliferative disease (MPD), unassociated with nutritional, metabolic, or endocrine disorders known to alter cholesterol metabolism. Multiple defects contributing to reduced total cholesterol have been found, including decreased plasma low density lipoproteins (LDL) with increased LDL catabolism, decreased high density lipoproteins (HDL), and reduced cholesterol content of both lipoprotein molecules. A reciprocal relation of spleen size and leukocyte count to plasma cholesterol has been observed. This research will explore the mechanisms responsible for hypocholesterolemia in MPD through in vivo and in vitro studies of lipoprotein metabolism, determine the relation of altered cholesterol metabolism to other features of hematic cell dysplasia, assess the value of lipoprotein cholesterol as a marker of disease activity, and determine whether hypocholesterolemia has an impact on the pathophysiology of MPD mediated by changes in cell membranes that may affect cell function. Regulation of cholesterol synthesis and lipoprotein receptor activity in cells originating from the neoplastic clone will be compared with that of autologous, non-clonally derived cells. The ontogeny of lipid metabolism in myeloid and monocytic lines will be studied in cultures of HL-60 cells. The effect of modification of clinical status, spontaneous or therapeutically induced, on deranged lipoprotein metabolism will be assessed by serial studies. The effect of chronic hypocholesterolemia on platelets and erythrocytes and the response to in vivo and in vitro manipulations that alter membrane cholesterol will be measured by platelet aggregation and erythrocyte deformability. Investigations of the chronic hypocholesterolemia of MPD will utilize an experiment of nature to elucidate the perturbations in the normal regulation of cholesterol metabolism that result from malignant forms of hematopoiesis and the impact of derangements in lipoprotein metabolism on cell function. Insights provided by these studies will lead to better understanding of the pathophysiology of MPD that may be translated into more rational approaches to clinical management.